Takotsubo cardiomyopathy (TCM) is also called stress-induced cardiomyopathy. It is a novel condition first identified in Japan, and is also known as stress cardiomyopathy. It has a presentation akin to acute coronary syndrome, but is non-ischemic in etiology.
Takotsubo syndrome is named after a type of octopus-trapping pot used by Japanese fishermen (tako – octopus, tsubo – pot). It refers to the occurrence of sudden stress-related cardiac weakening. The stressor may be physical, as occurs in almost 40% of cases, or emotional, in about a quarter of patients. The stressor may be chronic in some cases, with patients reporting constant but high-level anxiety preceding the attack. It almost always affects postmenopausal women and follows intense stress.
Introduction of Broken Heart Syndrome
The Japanese scientist Sato was the first to describe this strange condition under this name, in 1991, but even before this, others had noted that some people actually died of acute intense stress without evidence of any physical injury.
Following Sato’s publication, several cases were identified over a span of ten years, but this cardiomyopathy continued to be largely unknown in the West. Most of these papers were in Japanese, adding to the delay in recognition of this syndrome outside the country.
In 1989, a study reported the link between pheochromocytoma (an adrenal tumor resulting in very high levels of catecholamines in blood) and reversible left ventricular apical wall akinesis, which underlined the connection between high catecholamine levels and TCM. Reports and case series kept popping up in Japanese journals throughout the 1990s.
In 1997 another paper appeared describing reversible left ventricular dysfunction as a result of acute emotional stress. However, it was in 2001 that a Japanese-authored report on the condition appeared in a Western journal, naming it transient left ventricular apical ballooning.
On October 23, 2004, a huge earthquake (of 6.8 intensity on the Richter scale) occurred in Niigata Prefecture in Japan. Within a month, 16 people were diagnosed to have TCM. The majority were elderly women, and 13 of them lived near the epicenter. No less than 11 patients suffered TCM on the day of the earthquake. This report reached an audience which had already started to take note of this novel condition over the last few years.
Finally, in February 2005, the New England Journal of Medicine acknowledged the syndrome in its paper, paving the way for wider recognition of the broken heart syndrome. It explored the neurohumoral and clinical characteristics of stress cardiomyopathy.
The use of the name “broken heart syndrome”, to signify those who suffered this syndrome following the death of a loved one, attracted worldwide attention. This resulted in a rapid increase in the number of studies on TCM. After October 2011, the syndrome is being reported from almost every part of the world.
The evolution of the myocardial stunning hypothesis
In 1971, a study on 170 cases of sudden cardiac death was published, in all of which the role of sympathetic activation was prominent. That is, the patient was under intense stress, as a result of worry or anxiety, before the final event.
In 1980, Hirsch and Cebelin described a series of deaths following physical assault, in which the bodies showed no evidence of internal injury on post-mortem examination. Their study spanned 30 years, in in Cuyahoga county, Ohio. They reported that the myocardium showed contraction band necrosis and myofibrillar degeneration.
This was identical to that suffered by animals in conditions of intense stress, and was related to very high levels of catecholamines (such as norepinephrine and dopamine). They thus put forward the theory that stress caused elevation of catecholamine levels to produce lethal myofibrillar degeneration in man.
The Japanese scientists who were involved in the early work on this condition described it as the occurrence of an akinetic or hypokinetic segment in the heart extending from the apex of the heart to the mid-portion of the left ventricle but sparing the base of the heart. This was observed on left ventriculography, and led to the characteristic end-systolic appearance of the heart, resembling a wide-mouthed wide-bellied pot with a short narrow neck. The name "takotsubo syndrome" comes from the Japanese word for this kind of octopus trap, because the left ventricle takes on a shape resembling this fishing pot.
In short, the stress seems to trigger a surge of catecholamines which acts upon the myocardium in a variety of ways to reduce the contractility of the apical segment of the heart. For this reason, it was also known as apical akinesis syndrome. It is now accepted to be a cause of heart failure following acute stress, rarely resulting in serious complications such as ventricular arrhythmias or even ventricular rupture.
The exploration of Takotsubo pathophysiology
Though the etiology of this condition remains unclear, several hypotheses have cropped up. It is thought that spasm of several coronary vessels at epicardial level, or even deeper, may be one cause of the transient and reversible ischemia characteristic of this condition. Other similar situations include the reversible left ventricular dysfunction caused by pheochromocytoma, which shared the high catecholamine levels of Takotsubo syndrome.
Later work has built upon early research to show how this syndrome is linked with stress, but has conflicting characteristics when compared with an acute coronary syndrome:
Normal coronary vessels which show no signs of obstruction on angiography
Moderately elevated cardiac biomarker levels which fail to reach those levels which are characteristic of acute coronary syndromes
A hypokinetic left ventricular apex with a hypercontractile ventricular base, which is the benchmark of this condition
A very low acutely decreased ventricular ejection fraction at the time of presentation
Since the acknowledgment of this condition, a high level of clinical suspicion has led to the recognition of more and more cases.
Inverted Takotsubo syndrome
A recent paper describes an inverted form of Takotsubo syndrome with apical sparing and ventricular base hypokinesis, occurring at a young age in contrast to the postmenopausal age group affected by the classical syndrome. Much more research is required to elucidate the pathogenetic mechanisms which lead to these diverse clinical manifestations.
Reviewed by Alina Shrourou, BSc Further Reading